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Publication : linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis.

First Author  Maamar H Year  2013
Journal  Genes Dev Volume  27
Issue  11 Pages  1260-71
PubMed ID  23723417 Mgi Jnum  J:199178
Mgi Id  MGI:5500986 Doi  10.1101/gad.217018.113
Citation  Maamar H, et al. (2013) linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis. Genes Dev 27(11):1260-71
abstractText  Recently, researchers have uncovered the presence of many long noncoding RNAs (lncRNAs) in embryonic stem cells and believe they are important regulators of the differentiation process. However, there are only a few examples explicitly linking lncRNA activity to transcriptional regulation. Here, we used transcript counting and spatial localization to characterize a lncRNA (dubbed linc-HOXA1) located approximately 50 kb from the Hoxa gene cluster in mouse embryonic stem cells. Single-cell transcript counting revealed that linc-HOXA1 and Hoxa1 RNA are highly variable at the single-cell level and that whenever linc-HOXA1 RNA abundance was high, Hoxa1 mRNA abundance was low and vice versa. Knockdown analysis revealed that depletion of linc-HOXA1 RNA at its site of transcription increased transcription of the Hoxa1 gene cis to the chromosome and that exposure of cells to retinoic acid can disrupt this interaction. We further showed that linc-HOXA1 RNA represses Hoxa1 by recruiting the protein PURB as a transcriptional cofactor. Our results highlight the power of transcript visualization to characterize lncRNA function and also suggest that PURB can facilitate lncRNA-mediated transcriptional regulation.
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